Long-term and short-term exposures to ambient air pollutants, particularly particulate matter (PM), have been linked to cardiovascular disease (CVD). A number of factors, such as age and pre-existing disease, exacerbate the adverse cardiovascular effects of PM. Yet, it remains unclear whether the adverse cardiovascular effects of air pollution could be modified by diet and lifestyle factors. This is an important question because a large proportion of the general population is exposed to PM and CVD is the leading cause of death in US, accounting for 25.4% of the total deaths in the United States. We have an excellent opportunity to address this research gap by utilizing the National Health and Nutrition Examination Survey (NHANES) III Study, a well-established, nationally representative cohort, with detailed information on diet and lifestyle factors, blood biomarkers, and ambient air pollution. The main hypothesis is that diet can modify the adverse effect of air pollution on CVD morbidity and mortality. Obesity and high saturated fat intake are well established dietary and lifestyle factors associated with metabolic syndrome, a known risk factor for CVD. There is an increasing trend in the prevalence of metabolic syndrome in the U.S., and this may lead to future increases in CVD risk factors (Ford et al., 2004~ Johnson et al., 2009). Recent studies suggest that air pollution exposure is associated with increased levels of intermediate biomarkers of CVD, including metabolic syndrome (Chen, 2008), indicated by increased levels of blood cholesterols, blood pressure, and C-reactive protein in individuals exposed to high levels of PM. Therefore, it is hypothesized that the adverse relationships between ambient air pollutant exposure and CVD mortality are stronger in obese subjects, high saturated fat consumers, and insulin resistant people (i.e., individuals with metabolic syndrome). This hypothesis will be examined in 18,149 U.S. men and women in the NHANES III study cohort, who were enrolled in 1988-1994. Outdoor concentrations of PM and gaseous pollutants concentrations from nearest monitors within 5, 10, and 20 miles have been linked to each participant's residential address. Information on blood biomarkers, anthropometry, and dietary intake was obtained at study baseline and all subjects were followed up to 20 years until death and CVD mortality ascertained. These data will be used to explore the hypothesis that exposure to ambient air pollutant (in particular, PM) is associated with increased mortality as well as adverse changes in intermediate biomarkers of CVD and that these relationships are modified by adiposity and intake of calories from saturated fat. PUBLIC HEALTH RELEVANCE: We have assembled an interdisciplinary team of air pollution, nutrition, and genetics researchers to test our hypothesis that the adverse effects of ambient air pollution on the cardiovascular system are modified by nutrition factors. We will use the unique NHANES III data set to model the interaction of air pollution and diet on long term cardiac health effects, including mortality. Successful results will provide information on potential avenues for effect modification of the cardiac effects of air pollution by diet.